The current situation of maintenance (MT) after front-line therapy in non-transplant patients with multiple myeloma (MM) is not adequate in China. Hence, we conducted this multi-centered ...retrospective real-world study on efficacy and safety of the mainstream maintenance regimens, thalidomide (T-MT), lenalidomide (L-MT) and bortezomib (B-MT). Clinical data of newly diagnosed MM patients were collected from 9 centers of North China MM Registry from January 2010 to December 2020. The progression-free (PFS) and overall survival (OS) from maintenance, and adverse events were recorded.
A total of 316 patients were enrolled including 156 in T-MT, 113 in L-MT and 47 in B-MT. At baseline, the gender ratio, paraprotein isotype, ISS, R-ISS, and response evaluation before MT were comparable. Patients on L-MT were older. Greater proportions of patients in L-MT and B-MT had high-risk cytogenetic abnormalities (HRCA), defined as amplification 1q21 (1q21+), deletion 17p (17p-), t(4,14), t(14,16).
The median follow-up duration was 41.0, 21.9 and 20.7 months (m) in T-MT, L-MT and B-MT, respectively. Disease progression rate was 63.5%, 46% and 31.9%. Mortality rate was 29.5%, 19.5% and 8.5%. The median PFS was 23.7m in T-MT, compared with 23.5m in L-MT and 30.8m in B-MT (p=0.48). Median OS was 79.5m in T-MT, whereas not reached (NR) in the others (p=0.21). Patients reaching complete response (CR) or stringent CR (sCR) before MT had prolonged PFS compared to those with very good partial response (VGPR) or less in T-MT (28.7m vs 17.2m, p=0.048) and L-MT (29.9m vs 14.8m, p=0.01), while comparable in B-MT (NR vs 30.8, p=0.15). OS was similar despite of different response before MT. Patients with 1q21+ on T-MT had shorter PFS compared to those without (16.3m vs 22.8m, p=0.18), so did impaired median OS (53.1m vs 80.6m, p= 0.003). 1q21+ did not affect PFS in L-MT group (23.5m vs 27.4m, p=0.69), or B-MT (NR vs 30.8m, p=0.73). OS was not reached. Only a few patients with 17p-, yet also presented remarkably inferior PFS (6.8m vs 22.8m, p=0.007) and OS (32.3m vs 72.6m, p=0.02) in T-MT. PFS (15.6m vs 39.2 m, p=0.33) and OS (NR vs NR, p=0.83) were not of discrepancy in L-MT. In patients with any HRCA, T-MT resulted in shorter PFS (12.1m vs 22.8m, p=0.06) and OS (53.1m vs NR, p<0.01). While both were comparable in L-MT or B-MT, with HRCA or not. The main reason of MT withdrawal was disease progression. Discontinuation related to adverse events was seen in 5.1%, 5.8% and 0 patients in T-MT, L-MT and B-MT, respectively.
In this multi-centered real-world study, thalidomide, a response of CR or better predicts superior PFS in non-transplant NDMM. HRCAs drag down survival in thalidomide, while lenalidomide and bortezomib mostly reverse the negative effects. Though patients on L-MT and B-MT have greater proportion of HRCAs, PFS in three groups are comparable. Clinicians in the real practice prefer lenalidomide or bortezomib as maintenance in high-risk patients.
Maintenance therapy (MT) deepens response and prolongs progression free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) after frontline regimens. Ixazomib, a 2nd generation ...oral proteasome inhibitor, has been approved for MT because of the convenience and tolerability. We conducted this prospective multi-center study to compare the efficacy and safety of Ixazomib (I-MT) or Ixazomib plus Lenalidomide (IL-MT) to Lenalidomide (L-MT) as maintenance regimen in NDMM patients.
This study was approved by the Institutional Review Board of Peking Union Medical College Hospital and registered (NCT04217967). NDMM patients were enrolled from 10 centers of North China MM Registry, since September 2019. After 4 cycles of front-line induction therapy, patients reached partial response (PR) would receive autologous stem cell transplantation (ASCT) if eligible, or keep up to 5 cycles of front regimens if ineligible, then start MT. Patients did not reach PR would switch to 2nd-line induction for 2-5 cycles and start MT once PR was achieved. For MT, 4mg of Ixazomib was given on day 1,8,15, and 25mg of Lenalidomide every other day on days 1–21 of 28day cycles. Patients in dual drug group were administrated with both Ixazomib and Lenalidomide. The primary endpoint was PFS from MT.
A total of 111 patients were enrolled, including 45 in I-MT, 41 in L-MT and 25 in IL-MT. The demographic and clinical characteristics were comparable among three groups at baseline, including gender ratio, age, paraprotein isotype, ISS, R-ISS, response status before MT, and ASCT rate. Patients on IL-MT were slightly younger. The proportions of patients with high-risk cytogenetic abnormalities (HRCAs), defined as amplification 1q21, deletion 17p, t(4,14) and t(14,16), were comparable. The median follow-up duration since MT was 5.9, 13.5 and 5.3 months in I-MT, L-MT and IL-MT group, respectively. Disease progression rate was 4.4%, 12.2% and 8%. Mortality rate was 2.2%, 2.4% and 0. There were 84%, 88.8% and 80% of the patients reached VGPR or better before MT, while the rates improved to 95%, 84% and 92% during follow-up. The prevalence of peripheral neuropathy with grade 1 was 20% on I-MT, 36% on IL-MT and 4.9% on L-MT. No grade 2 PN or higher was recorded. The incidence of gastrointestinal events was 11.1%, 24% and 0, respectively. All hematologic toxicities were lower than 8%. Infection rates were 8.9%, 4% and 7.3%. Skin rashes were more common in lenalidomide containing regimens (2.2%, 8% and 7.3%). No drug withdrawal was related to adverse events.
Due to inadequate access to melphalan and low rate of ASCT in China, there is still a gap of PFS in NDMM patients with those in western countries. We herein design this multi-centered prospective study to evaluate if dual drug MT will further strengthen response and make up the gap. Though the primary endpoint–PFS has not been reached in all treatment groups, dual MT improves response most and is quite tolerable.
Banana is an important tropical fruit and China is the world’s third largest banana producer. The standardization level of banana industry not only affects the yield and quality of banana,but also ...plays an important role in promoting the production standardization and industrialization of other tropical crops. Through the analysis of revision,publicity and implementation of banana standard system in China as well as the study on its standard system and quality and safety standards,it is found that there are some problems such as irrational banana standard structure,short period of validity of standard,low level of quality and safety standards,and loose link between standards and production. At the same time,some recommendations are put forward in order to guide the standardized production and trade,research and management of banana and promote sustained,healthy and stable development of the banana industry in China.
Banana is an important economic crop and food crop in tropical and subtropical areas. It is the fruit with the largest production, trade volume and trade value among the fresh fruits in the world. ...The sustainable development of banana industry is of great significance to promote the rural revitalization in China and even the agricultural economic development in the tropical areas of the world. The main banana producing and exporting countries are mainly concentrated in Asia and America. In 2020, the harvested area and production of bananas in the world were 5.203 5 million ha and 119.8337 million t respectively, which increased by 24.58% and 72.57%, respectively compared with that in 2001. The main producing countries were India, China, Indonesia, Brazil and Ecuador. At present, there are about 200 countries or regions importing bananas in the world. In 2020, the world's banana import value and import quantity were 233 761 million t and 15.607 billion USD respectively, increasing by 71.42% and 165.06% respectively compared with 2001. The main importing countries are the United States of America, China, Russia, Germany and Finland. In 2020, the export volume and value of bananas in the world were 24.497 million t and 13.356 billion USD, respectively, increasing by 67.93% and 218.03%, respectively compared with 2001. The main exporting countries are Ecuador, Costa Rica, Guatemala, Colombia and the Philippines. China is the second largest banana producer and importer in the world. In 2020, the production and import volume of bananas were separately 11.872 6 million t and 1.819 2 million t, accounting for 9.91% and 7.78% of the world. According to the forecast of banana production and trade data of the FAO, the world banana production and trade volume are forecast to show a steady growth trend. And it is predicted that the world banana production, import and export volume will reach 159.6448 million t, 31.051 4 million t and 32.194 1 million t, respectively in 2030, increasing by 33.22%, 32.83% and 31.42%, respectively compared with 2020. At the same time, the world banana industry is facing challenges such as global climate change, banana wilt and soil acidification in banana planting areas. Carrying out breeding cooperation of banana varieties with disease resistance, stress resistance and high yield, and strengthening joint research and development of green, high-quality and efficient banana production technology, will contribute to the sustainable development of banana industry and promote the banana quality safety and world food security.
The brain-gut-microbiome axis has emerged as an important pathway through which perturbations in the gut and/or microbial microenvironment can impact neurological function. Such alterations have been ...implicated in a variety of neuropsychiatric disorders, including depression, anxiety, and Alzheimer's Disease (AD) and the use of probiotics as therapy for these diseases remains promising. However, the mechanisms underlying the gut microenvironment's influence on disease pathogenesis and therapy remain unclear.
The objective of this study is to investigate the effect of a novel probiotic formula, BIOCG, on cognitive function and pathobiological mechanisms, including amyloid processing and dendritic spine dynamics, in a mouse model of AD.
BIOCG was administered for 3 months to 3xTg or 3xTg; Thy1-YFP AD mice and functional outcomes were assessed via behavioral testing and electrophysiology. Mechanisms relevant to AD pathogenesis including dendritic spine morphology and turnover, Amyloid Precursor Protein (APP) processing and microglial phenotype were also evaluated. Finally, we sequenced fecal samples following probiotic treatment to assess the impact on gut microbial composition and correlate the changes with the above described measures.
Mice treated with BIOCG demonstrated preserved cognitive abilities and stronger Long- Term Potentiation (LTP), spontaneous Excitatory Postsynaptic Currents (sEPSC), and glutamate-induced LTPs, indicative of functional and electrophysiological effects. Moreover, we observed attenuated AD pathogenesis, including reduced Amyloid Beta (Aβ) burden, as well as more mature dendritic spines in the BIOCG-treated. Our finding of changes in microglial number and phenotype in the treatment group suggests that this formulation may mediate its effects via attenuation of neuroinflammation. Sequencing data confirmed that the gut microbiome in treated mice was more varied and harbored a greater proportion of "beneficial" bacteria.
Overall, our results indicate that treatment with BIOCG enhances microbial diversity and, through gut-brain axis interactions, attenuates neuroinflammation to produce histologic and functional improvement in AD pathogenesis.
Banana is an important tropical fruit and China is the world's third largest banana producer. The standardization level of banana industry not only affects the yield and quality of banana, but also ...plays an important role in promoting the production standardization and industrialization of other tropical crops. Through the analysis of revision, publicity and implementation of banana standard system in China as well as the study on its standard system and quality and safety standards, it is found that there are some problems such as irrational banana standard structure, short period of validity of standard, low level of quality and safety standards, and loose link between standards and production. At the same time, some recommendations are put forward in order to guide the standardized production and trade, research and management of banana and promote sustained, healthy and stable development of the banana industry in China.
Microplastics (MPs), the appearance of which has gained considerable interest, can act as vectors to transport other pollutants such as metals into organisms. In this study, the sorption isotherms of ...three model heavy metals (i.e., Cu2+, Cd2+, and Pb2+) on four virgin plastic particles including chlorinated polyethylene (CPE), PVC, and two polyethylene plastic particles (i.e., LPE and HPE). HPE and LPE were investigated. The results showed that MPs can load high amounts of Pb2+, Cu2+ and Cd2+. The sorption affinity of the three metals to the model MPs followed the sequence of CPE > PVC > HPE > LPE. The adsorption process was affected by the chemical structure and electronegativity of the sorbents, and seemed irrelevant to the crystallinity of MPs. For the three metals, Pb2+ exhibited significantly stronger sorption than did Cu2+ and Cd2+ due to the strong electrostatic interaction. Moreover, pH can significantly affect the sorption of metals on MPs, but ionic strength exerted a relatively slight effect on this process. In brief, the electrostatic interaction played an important role in the sorption of Pb2+ to model MPs. For Cd2+ and Cu2+, sorption was determined by electrostatic interaction together with surface complexation onto the plastic surface. This study indicates that depending on the surface physicochemical properties of MPs the adsorption behavior can vary significantly. Therefore, the adsorption process of metals on MPs should be readily affected by other environmental mediums in the environment. The study provides additional insight into the behavior of MPs as a vector of metals.
•Sorption of Cu2+, Cd2+, and Pb2+ on four virgin plastic particles was investigated.•The sorption strength followed the order of Pb2+>Cu2+>Cd2+.•PH and ionic strength can affect the sorption of metals on MPs.•Electrostatic interaction played an important role in the sorption of Pb2+ to MPs.•Electrostatic interaction and complexation determined the sorption of Cd2+ and Cu2+.
Flexible and stretchable physical sensors capable of both energy harvesting and self‐powered sensing are vital to the rapid advancements in wearable electronics. Even so, there exist few studies that ...can integrate energy harvesting and self‐powered sensing into a single electronic skin. Here, a stretchable and washable skin‐inspired triboelectric nanogenerator (SI‐TENG) is developed for both biomechanical energy harvesting and versatile pressure sensing. A planar and designable conductive yarn network constructed from a three‐ply‐twisted silver‐coated nylon yarn is embedded into flexible elastomer, endowing the SI‐TENG with desired stretchability, good sensitivity, high detection precision, fast responsivity, and excellent mechanical stability. With a maximum average power density of 230 mW m−2, the SI‐TENG is able to light up 170 light‐emitting diodes, charge various capacitors, and drive miniature electronic products. As a self‐powered multifunctional sensor, the SI‐TENG is adopted to monitor human physiological signals, such as arterial pulse and voice vibrations. Furthermore, an intelligent prosthetic hand, a self‐powered pedometer/speedometer, a flexible digital keyboard, and a proof‐of‐concept pressure‐sensor array with 8 × 8 sensing pixels are successively demonstrated to further confirm its versatile application prospects. Based on these merits, the developed SI‐TENG has promising applications in wearable powering technology, physiological monitoring, intelligent prostheses, and human–machine interfaces.
A flexible, stretchable, washable, and multifunctional triboelectric‐based electronic skin obtained by embedding a planar and designable yarn electrode network into transparent elastomer is presented for both biomechanical energy harvesting and self‐powered pressure sensing. An energy harvester, physiological monitor, prosthetic hand, real‐time pedometer/speedometer, flexible digital keyboard, and tactile sensing array are successively demonstrated in order to confirm its versatile application prospects.
As the frequency and intensity of storms increase, a growing need exists for resilient shore protection techniques that have both environmental and economic benefits. In addition to producing ...seafood, aquaculture farms may also provide coastal protection benefits either alone or with other nature-based structures. In this paper, a generalized three-layer frequency dependent theoretical model is derived for random wave attenuation due to presence of biomass within the water column. The biomass can be characterized as submerged, emerged, suspended and floating canopies that can consist of natural aquatic vegetation with potential aquaculture systems of kelp or mussels. The present analytical solutions can reduce to the solutions by Mendez and Losada (2004), Chen and Zhao (2012) and Jacobsen et al. (2019) for submerged rigid aquatic vegetation. The present theoretical model incorporates the motion of these canopies using a cantilever-beam model for slender components and a buoy-on-rope model for elements with concentrated mass and buoyancy. Analytical results are compared with existing laboratory and field datasets for submerged and suspended canopies. The theoretical model was then used (in a case study at a field site in Northeastern US) to investigate the capacity of suspended mussel farms with submerged aquatic vegetation (SAV) to dissipate wave energy during a recent storm event. Compared to a dense SAV meadow in shallower water, the suspended aquaculture farms more effectively attenuate random waves with a smaller peak period and the higher frequency components of wave spectrum. The performance of suspended aquaculture farms is less affected by water level changes due to tides, surge and sea level rise, while the wave attenuation performance of SAV decreases with increasing water level due to decreased wave motion near the sea bed. Incorporating suspended aquaculture farms offshore significantly enhance the coastal protection effectiveness of SAV-based living shorelines and extend the wave attenuation capacity over a wider wave period and water level range. The combination of suspended aquaculture farms and traditional living shorelines provides a more effective nature-based coastal defense strategy than the traditional living shorelines alone.
•Frequency dependent analytical solutions for wave attenuation by flexible canopies.•Analytical solutions for canopy motion with cantilever-beam and buoy-on-rope models.•Suspended aquaculture farms reduce short waves and are less affected by water depth.•Aquaculture farms enhance the coastal defense of SAV-based living shorelines.
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